The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger
Open accessAbstract
A considerable number of studies demonstrate that acute and chronic stressors prime CNS innate immune responses to subsequent pro-inflammatory challenges and that glucocorticoids mediate, in part, stress-induced sensitization of pro-inflammatory immune responses. Here, we explore the notion that GCs produce a persisting sensitization of CNS innate immune effectors (e.g. microglia) so that they will generate a potentiated pro-inflammatory response after the GC rise has dissipated, thereby enhancing the sickness response to infection or injury and maximizing the animal's ability to neutralize danger. The stress-induced GC response is conceptualized here as an neuroendocrine warning signal or alarmin to the innate immune system, which prepares or sensitizes the innate immune response to potential danger. Thus, a new understanding of the stress response and its function (priming CNS innate immune responses to infection or injury during a fight/flight emergency) would be suggested.
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“In primitive organisms threats engage defensive reflexes (Walters & Erickson, 1986).”
From Learned helplessness at fifty: Insights from neuroscience. (2016) · cites this paper as Frank, Watkins, & Maier, 2013
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“This process can become self-perpetuating because chronically elevated glucocorticoids can stimulate production of neuroinflammation by activating microglia (Frank et al., 2013; Nair and Bonneau, 2006), the resident immune cells of the brain.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Frank et al., 2013
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“However, the well-studied mediators of stress physiology, glucocorticoids and catecholamines, are primarily thought to be immunosuppressive (Russell and Lightman, 2019) and used therapeutically for this purpose, creating a paradox that many have tried to resolve for over 30 years (Frank et al., 2013; Munck et al., 1984).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Frank et al., 2013
In the citing paper
“A number of mediators of the stress response, most notably noradrenaline and glucocorticoids, have been found to mediate the effects of stress on neuroinflammatory processes (Frank et al, 2013;Wohleb et al, 2011).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Frank et al, 2013
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Metadata
- Authors
- Frank, M. G., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Frank, Matthew G.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 33
- Pages
- 1-6
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC5652304
- OpenAlex
- W2025373842
- Cited by
- 160
- References
- 67
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 18 · 2019: 13 · 2018: 18 · 2017: 14 · 2016: 17 · 2015: 18 · 2014: 9 · 2013: 4
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (F32DA015591)
- National Institute of Dental and Craniofacial Research (R01DE021966)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- microglia, alarmins, threat detection, stress response, glucocorticoid feedback
- MeSH terms
- Animals, Brain, Central Nervous System, Disease Models, Animal, Glucocorticoids, Humans, Immunity, Innate, Neuroimmunomodulation, Signal Transduction, Oxidative Stress
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